Ozone, Heat Wave, and Cardiovascular Disease Mortality: A Population-Based Case-Crossover Study.

A case-crossover study among 511,767 cardiovascular disease (CVD) deaths in Jiangsu province, China, during 2015-2021 was conducted to assess the association of exposure to ambient ozone (O3) and heat wave with CVD mortality and explore their possible interactions. Heat wave was defined as extreme high temperature for at least two consecutive days. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential O3 and heat wave exposures were assessed using grid data sets (spatial resolution: 1 km × 1 km for O3; 0.0625° × 0.0625° for heat wave). Conditional logistic regression models were applied for exposure-response analyses and evaluation of additive interactions. Under different heat wave definitions, the odds ratios (ORs) of CVD mortality associated with medium-level and high-level O3 exposures ranged from 1.029 to 1.107 compared with low-level O3, while the ORs for heat wave exposure ranged from 1.14 to 1.65. Significant synergistic effects on CVD mortality were observed for the O3 and heat wave exposures, which were generally greater with higher levels of the O3 exposure, higher temperature thresholds, and longer durations of heat wave exposure. Up to 5.8% of the CVD deaths were attributable to O3 and heat wave. Women and older adults were more vulnerable to the exposure to O3 and heat wave exposure. Exposure to both O3 and heat wave was significantly associated with an increased odds of CVD mortality, and O3 and heat wave can interact synergistically to trigger CVD deaths.

Babaodan overcomes cisplatin resistance in cholangiocarcinoma via inhibiting YAP1.

CONTEXT: Cholangiocarcinoma with highly heterogeneous, aggressive, and multidrug resistance has a poor prognosis. Although babaodan (BBD) combined with cisplatin improved non-small cell lung cancer efficacy, its impact on overcoming resistance in cholangiocarcinoma remains unexplored. OBJECTIVE: This study explored the role and mechanism of BBD on cisplatin resistance in cholangiocarcinoma cells (CCAs). MATERIALS AND METHODS: Cisplatin-resistant CCAs were exposed to varying concentrations of cisplatin (25-400 µg/mL) or BBD (0.25-1.00 mg/mL) for 48 h. IC50 values, inhibition ratios, apoptosis levels, DNA damage, glutathione (GSH) levels, oxidized forms of GSH, total GSH content, and glutaminase relative activity were evaluated using the cell counting kit 8, flow cytometry, comet assay, and relevant assay kits. RESULTS: BBD-reduced the cisplatin IC50 in CCAs from 118.8 to 61.83 µg/mL, leading to increased inhibition rate, apoptosis, and DNA damage, and decreased expression of B-cell lymphoma-2, p-Yes-associated protein 1/Yes-associated protein 1, solute carrier family 1 member 5, activating transcription factor 4, and ERCC excision repair 1 in a dose-dependent manner with maximum reductions of 78.97%, 51.98%, 54.03%, 56.59%, and 63.22%, respectively; bcl2-associated X and gamma histone levels were increased by 0.43-115.77% and 22.15-53.39%. The impact of YAP1 knockdown on cisplatin-resistant CCAs resembled BBD. GSH, oxidized GSH species, total GSH content, and glutaminase activity in cisplatin-resistant CCAs with BBD treatment also decreased, while YAP1 overexpression countered BBD's effects. DISCUSSION AND CONCLUSION: This study provides a scientific basis for BBD clinical application and provides a new direction for BBD biological mechanism research.

Association between healthy lifestyle factors and health-related quality of life among Chinese adolescents: the moderating role of gender.

BACKGROUND: To examine the associations of the independent and combined healthy lifestyle factors with health-related quality of life (HRQOL) in adolescents, and to test the moderating role of gender. METHODS: This cross-sectional study included 5125 adolescents aged between 11 and 20 years. They provided self-reported data on six healthy lifestyle factors, including never smoking, never drinking, good sleep quality, sufficient sleep duration, appropriate Internet use, and adequate physical activity. Adolescents' HRQOL was evaluated using the Pediatric Quality of Life Inventory version 4.0. Linear regression models were conducted to explore the association of individual and combined healthy lifestyle factors with adolescents' HRQOL. We further performed stratified analyses and likelihood ratio test to explore the moderating role of gender in these associations. RESULTS: Of the included adolescents, the proportions with 0-2, 3, 4, and 5-6 healthy lifestyle factors were 13.6%, 26.4%, 44.3%, and 15.7%, respectively. Compared to adolescents with composite healthy lifestyle scores of 0-2, those with scores of 3, 4, or 5-6 had significantly higher HRQOL scores across all dimensions, summary scales, and total scale in both unadjusted and adjusted models. Specifically, adolescents with 5-6 healthy lifestyle factors had a total scale score that was 19.03 (95%CI: 17.76 to 20.30) points higher than their counterparts who only had 0-2 healthy lifestyle factors. Significant dose-response patterns were also observed in aforementioned associations. Gender was a significant moderator in the associations between composite healthy lifestyle groups and HRQOL scores, except for the social functioning dimension. CONCLUSIONS: Our results confirmed that combined healthy lifestyle factors were associated with improved HRQOL among adolescents, with a stronger association observed in girls. These findings underscore the necessity for education and healthcare authorities to design health-promoting strategies that encourage multiple healthy lifestyle factors in adolescents, with the objective of enhancing their overall health outcomes.

Numb inhibits migration and promotes proliferation of colon cancer cells via RhoA/ROCK signaling pathway repression.

Numb regulates cell proliferation and differentiation through endocytosis and ubiquitination of signaling molecules. Besides, Numb controls the migration of epithelial cells by regulating intercellular junctions. Studies have shown that Numb promotes or inhibits tumor progression in different tumors. However, its role and mechanism in colorectal cancer remain unclear. We found that the expression level of Numb in colon tumor tissues has a great variety in different patients. Numb expression was negatively correlated with TNM stage and lymph node metastasis but positively correlated with tumor size. Elevated expression of Numb was associated with a good prognosis. Inhibiting Numb expression promoted the migration and invasion of colon cancer cells induced by TGF-ß, up-regulated the expression of EMT-related molecule Snail, and prevented the expression of E-cadherin. We also found that Numb promoted the proliferation and clones formation while inhibiting colon cancer cells' late apoptosis. In addition, Numb inhibited the RhoA activation and ROCK inhibitor Y-27632 or interfered with ROCK expression, partially inhibiting Numb-regulated cell proliferation and migration. In vivo tumorigenesis assay in nude mice also found that Numb promoted the proliferation of colon cancer cells, inhibited the expression of E-cadherin, and strengthened the expression of Snail. In conclusion, our study found that Numb plays multiple roles in the occurrence and progression of colon cancer by regulating the RhoA/ROCK signaling pathway, which provides a new theoretical molecular basis for the pathogenesis of colon cancer.

Pathological evaluation of renal complications in children following allogeneic hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients. METHODS: We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years. RESULTS: Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m2) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria. CONCLUSIONS: This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.

Association of childhood threat and deprivation with depressive symptoms and the moderating role of current economic status among middle-aged and older adults in China.

PURPOSE: To investigate the independent impact of threat-related and deprivation-related adverse childhood experiences (ACEs) on depressive symptoms among middle-aged and older adults, and to evaluate the moderating role of current economic status in these associations. METHODS: This cross-sectional study included 11,048 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. We captured five threat-related ACEs and five deprivation-related ACEs by questionnaires. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale. Current economic status was reflected by annual per capita household consumption expenditure. We performed logistic regression analyses to evaluate the independent association of childhood threat and deprivation with depressive symptoms, and conducted stratified analyses and tests for interaction to explore the moderation effect of current economic status in such associations. RESULTS: Compared with the nonexposed group, the experience of both childhood threat and deprivation were independently associated with greater risks of depressive symptoms later in life (odds ratio [OR] 1.75, 95% CI 1.49-2.05 for ≥ 2 threat-related ACEs; OR 2.02, 95% CI 1.67-2.43 for ≥ 2 deprivation-related ACEs). High current economic status significantly ameliorated the impact of childhood deprivation, but not threat, on depressive symptoms (P value for interaction 0.038). CONCLUSIONS: Both threat-related and deprivation-related ACEs were associated with the risk of depressive symptoms among middle-aged and older adults, while current economic status was a significant moderator in such risks only for childhood deprivation. The findings implied that prioritising targeted interventions for individuals with ACEs, especially for childhood deprivation victims who were economically disadvantaged in adulthood, may help mitigate depressive symptoms in later life.

Critical window for the association between early electronic screen exposure and hyperactive behaviors in preschool children.

Electronic screens have become an integral part of modern life, accompanied with growing concerns for children's neuropsychological development. This study aimed to evaluate the associations between measures of early life screen exposure and hyperactive behaviors among preschool children. The study also aimed to investigate their cumulative effects and the critical window for these associations. A cross-sectional survey was conducted among 52 625 mother-child dyads at preschools in LongHua District of Shenzhen, China. A self-administered structured questionnaire was used to assess socio-demographic characteristics, duration of children's electronic screen exposure in each of the first 3 years following birth and the presence of current hyperactive behaviors. A series of logistic regression models were used to examine the relationship between previous screen time and current hyperactive behaviors. A crossover analysis was used to explore the critical window for a significant relationship between screen time and hyperactive behaviors. We found that exposure to electronic screens in the first 3 years of life was associated with hyperactive behaviors in preschool children. A cumulative effect was shown in children with an average daily screen time less than 60 min, with adjusted ORs increasing from 1.262 to 1.989 as screen exposure years increased from 1 to 3 years. A critical window was identified in that children in the first 2 years after birth were vulnerable to electronic screen exposure. Exposure to televisions, mobile phones, and computers were all related to elevated risks for hyperactive behaviors. In conclusion, early screen exposure appears to increase the risk for hyperactive behaviors in preschool children with the presence of a cumulative effect, a critical window and different electronic screens having similar effects.

Parent-child interactions in early life mediating association between prenatal maternal stress and autistic-like behaviors among preschoolers.

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

Network meta-analysis of the optimal time of applying enteral immunonutrition in esophageal cancer patients receiving esophagectomy.

BACKGROUND: Enteral immunonutrition (EIN) has been extensively applied in cancer patients; however, its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN. METHODS: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Meta-analysis with head-to-head approach and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 software. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes. RESULTS: Total 14 studies involving 1071 patients were included. Meta-analysis with head-to-head approach indicated no difference between EIN regardless of the application time and standard EN (SEN); however, subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR = 0.47; 95%CI = 0.26 to 0.84; p = 0.01) and pneumonia (OR = 0.47; 95%CI = 0.25 to 0.90; p = 0.02) and shortened the length of hospitalization (LOH) (MD = - 1.01; 95%CI = - 1.44 to - 0.57; p < 0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes. CONCLUSIONS: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/KJ9UY.

Critical window for the association between prenatal environmental tobacco smoke exposure and preterm birth.

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.

Association between prenatal exposure to indoor air pollution and autistic-like behaviors among preschool children.

Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources.

Adverse childhood experiences and handgrip strength among middle-aged and older adults: a cross-sectional study in China.

BACKGROUND: Evidence on the association between adverse childhood experiences (ACEs) and handgrip strength (HGS) in later life was limited and inconclusive. We aimed to explore the impact of ACEs on HGS among middle-aged and older Chinese adults. METHODS: We conducted a cross-sectional study with data extracted from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey with respondents recruited from 450 villages/urban communities of 28 provinces. Participants aged 45 years or older were drawn from the CHARLS 2014 life history survey and the 2015 health survey. Twelve ACE indicators before the age of 17 years were collected. HGS was measured with a dynamometer and the maximum value of HGS obtained from both hands was used in the analyses. Low muscle strength (LMS) was defined according to the recommendation of European Working Group on Sarcopenia in Older People (EWGSOP). Multivariate linear and logistic regression models were constructed to evaluate the association of ACEs with continuous HGS and LMS, with adjustment for age, sex, marital status, ethnicity, area of residence, smoking and drinking status, body mass index, hypertension, dyslipidaemia, diabetes mellitus, cardiovascular disease, arthritis, hip fracture, and memory-related disease. RESULTS: Of the 7209 eligible participants, 2258 (31.3%) had experienced three or more ACEs. Compared to individuals without ACEs, exposure to ≥ 3 ACEs was negatively associated with continuous HGS in kilogram (ß = -0.93, 95% CI: -1.37, -0.49) and positively associated with the risk of LMS (OR = 1.34, 95% CI: 1.12, 1.61). Such associations were consistently found both in men and women who had experienced three or more ACEs. Significant dose-response relationship between the number of ACEs and outcomes was also observed in the overall population and different sex groups. CONCLUSION: Exposure to ACEs was associated with lower HGS and increased risk of LMS among middle-aged and older Chinese adults, indicating the importance of intervention in individuals with experience of ACEs in order to mitigate its detrimental impact on HGS and promote healthy ageing.

Comorbid depression and obesity, and its transition on the risk of functional disability among middle-aged and older Chinese: a cohort study.

BACKGROUND: Evidence has indicated that depression and obesity were associated with functional disability, independently. However, little is known about the detrimental impact of comorbid depression and obesity, as well as its transition on functional disability. This study investigated the association of baseline depression-obesity status and its dynamic change with incident functional disability among middle-aged and older Chinese. METHODS: This cohort study included 5507 participants aged ≥45 years from the 2011 and 2015 waves of China Health and Retirement Longitudinal Study. Depression was defined with a score ≥ 10 using the 10-item Centre for Epidemiologic Studies Depression Scale. Obesity was defined as body mass index ≥28 kg/m2. Participants were cross-classified by depression and obesity status at baseline, and its change during follow-up. Logistic regression models were constructed to evaluate the association of baseline depression-obesity status and its transition with incident functional disability defined by the Katz index of activities of daily living scale. RESULTS: Over four-year follow-up, 510 (9.3%) participants developed functional disability. Individuals with baseline comorbid depression and obesity had the highest risk of functional disability (OR = 2.84, 95% CI: 1.95-4.15) than non-depressive participants without obesity, or those with depression or obesity alone. When investigating the dynamic changes of depression-obesity status on functional disability incidence, those with stable comorbidity throughout two surveys had the greatest risk of functional disability (OR = 4.06, 95% CI: 2.11-7.80). Progression of depression-obesity status was associated with increased risk of functional disability, while regression from baseline to follow-up was linked to attenuated risk estimates. CONCLUSIONS: Among middle-aged and older Chinese adults, the risk of functional disability was exaggerated with comorbid depression and obesity. Our data further suggest that transitions of depression and obesity over time are associated with the risk of developing functional disability.

Associations of excessive screen time and early screen exposure with health-related quality of life and behavioral problems among children attending preschools.

BACKGROUND: Both excessive screen time and early screen exposure have been linked to children's health outcomes, but few studies considered these two exposures simultaneously. The aim of this study was to explore the independent and interactive associations of excessive screen time and early screen exposure with health-related quality of life (HRQOL) and behavioral problems among Chinese children attending preschools. METHODS: A cross-sectional study of 4985 children aged between 3 and 6 years was conducted in Chengdu, China. Each parent has finished an online questionnaire regarding their children's screen use, HRQOL, and behavioral problems. Children with screen time over 1 h/day were considered as having excessive screen time. Early screen exposure was defined if the children had started using screen-based media before the age of 2 years. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0), while behavioral problems were confirmed with the 48-item Conners' Parent Rating Scale (CPRS-48). RESULTS: Of the 4985 children (2593 boys and 2392 girls) included, the mean age was 4.6 (SD: 1.0) years. After adjustment for confounders and early screen exposure, excessive screen time was significantly associated with worse HRQOL scores in all dimensions and summary scales, as well as each type of behavioral problems (all p values < 0.05). We also found that compared to children with later initiation of screen exposure, those with screen use before the age of 2 years had significantly lower emotional functioning score (ß: - 2.13, 95%CI: - 3.17, - 1.09) and psychosocial health summary score (ß: - 0.82, 95%CI: - 1.54, - 0.10) of HRQOL, as well as higher risks of conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, and hyperactivity index, which were independent of excessive screen use. Furthermore, there were significant interactive effects of excessive screen time and early screen exposure on emotional functioning domain of HRQOL scores and conduct problems. CONCLUSION: Excessive screen time and early screen exposure are two independent and interactive factors to children's HRQOL and behavioral problems. Our findings support current guidelines to limit screen exposure in children. Appropriate screen use may represent an important intervention target to improve children's HRQOL and reduce their behavioral problems.

Association of healthy lifestyle with risk of obstructive sleep apnea: a cross-sectional study.

BACKGROUND: No studies investigated the whole effect of modifiable lifestyle factors on OSA risk. This study aimed to examine the individual and combined effects of lifestyle factors on OSA risk among Chinese adults. METHODS: This cross-sectional study included 9733 participants aged 35 to 74 years from the baseline survey of Guangzhou Heart Study. OSA was evaluated by Berlin Questionnaire. The healthy lifestyle score (HLS), representing the overall effect of lifestyles, was derived from seven lifestyle factors: active smoking, passive smoking, alcohol, diet, waist-hip ratio, leisure-time physical activity, and mental status. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model. RESULTS: 8107 participants were divided into the non-OSA group and 1626 participants into the OSA group. No passive smoking (OR 0.83, 95% CI 0.74-0.94), healthy waist-hip ratio (OR 0.67, 95% CI 0.58-0.77) and healthy mental status (OR 0.45, 95% CI 0. 29-0.73) were associated with a reduced risk of OSA after adjusting for confounders, while others not. Participants with higher HLS were negatively associated with OSA risk (P-trend < 0.001). In comparison to the participants with 0-3 HLS, the OR for participants with 4, 5, 6, and 7 HLS was 0.68 (95% CI 0.56-0.84), 0.71 (95% CI 0.59-0.86), 0.62 (95% CI 0.51-0.76) and 0.49 (95% CI 0.37-0.65) after adjusting for confounders. Every 1-score increment of HLS was associated with a 13% lower risk of OSA. CONCLUSIONS: The results suggest that HLS reflecting the combined effect of multiple-dimensional lifestyle factors was inversely associated with OSA risk. Preventive strategies integrating multiple lifestyle factors may provide a more feasible approach for OSA prevention.

Association between systemic inflammation and activities of daily living disability among Chinese elderly individuals: the mediating role of handgrip strength.

BACKGROUND: Aging is accompanied by chronic low-grade inflammation (inflammaging), which is a risk factor for low handgrip strength (HGS) and activities of daily living (ADL) disability. AIMS: To explore the association between C-reactive protein (CRP) and ADL disability in Chinese elderly individuals and to further evaluate the mediating role of HGS in this association. METHODS: We used data from the China Health and Retirement Longitudinal Study (CHARLS) that were collected in 2015. A total of 3601 elderly individuals aged ≥ 60 years were included. Baron and Kenny's causal steps method was used to explore the possible mediating role of HGS in the associations between CRP and ADL disability. Karlson-Holm-Breen method was further applied to decompose total effect into direct effect and indirect effect via HGS. Subgroup analysis was conducted by sex and age. RESULTS: A high level of CRP (≥ 3 mg/L) was significantly associated with ADL disability after adjustment for covariates (OR = 1.50, 95% CI = 1.17-1.94). After introducing HGS into the model, the risk estimate was reduced but still significant (OR = 1.40, 95% CI = 1.08-1.81). The proportional mediation through HGS was 14.71%. Similar results were observed in both sexes and in participants aged < 70 years. CONCLUSION: CRP was positively associated with the risk of ADL disability in Chinese elderly individuals, and this association was mediated by HGS. Improving muscle strength in combination with anti-inflammatory treatment may have a beneficial effect to maintain ADL ability. Further randomized controlled trials on this topic are necessary.

A clinical model and nomogram for early prediction of gestational diabetes based on common maternal demographics and routine clinical parameters.

AIM: We aimed to develop a risk prediction model for gestational diabetes mellitus (GDM) based on the common maternal demographics and routine clinical variables in Chinese population. METHODS: Individual information was collected from December 2018 to October 2019 by a pretested questionnaire on demographics, medical and family history, and lifestyle factors. Multivariable logistic regression was performed to establish a predictive model for GDM by variables in pre- and early pregnancy. The consistency and discriminative validity of the model were evaluated by Hosmer-Lemeshow goodness-of-fit testing and ROC curve analysis. Internal validation was appraised by fivefold cross-validation. Clinical utility was assessed by decision curve analysis. RESULTS: Total 3263 pregnant women were included with 17.2% prevalence of GDM. The model equation was: LogitP = -11.432 + 0.065 × maternal age (years) + 0.061 × pre-pregnancy BMI (kg/m2 ) + 0.055 × weight gain in early pregnancy (kg) + 0.872 × history of GDM + 0.336 × first-degree family history of diabetes +0.213 × sex hormone usages during pre- or early pregnancy + 1.089 × fasting glucose (mmol/L) + 0.409 × triglycerides (mmol/L) + 0.082 × white blood cell count (109/L) + 0.669 × positive urinary glucose. Homer-Lemeshow goodness-of-fit testing indicated a good consistency between predictive and actual data (p = 0.586). The area under the ROC curve (AUC) was 0.720 (95% CI: 0.697 ~ 0.744). Cross-validation suggested a good internal validity of the model. A nomogram has been made to establish an easy to use scoring system for clinical practice. CONCLUSIONS: The predictive model of GDM exhibited well acceptable predictive ability, discriminative performance, and clinical utilities. The project was registered in clinicaltrial.gov.com with identifier of NCT03922087.

Oral sulfate solution benefits polyp and adenoma detection during colonoscopy: Meta-analysis of randomized controlled trials.

OBJECTIVES: Although oral sulfate solution (OSS) has been revealed to be not only safe and efficacious but also noninferior to polyethylene glycol with ascorbic acid (PEG + ASC), it is unclear whether OSS can ultimately increase the polyp detection rate (PDR) and adenoma detection rate (ADR). We performed this meta-analysis to estimate the effect of OSS on PDR and ADR during colonoscopy. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) investigating the comparative effect of OSS versus PEG + ASC on the PDR and ADR during colonoscopy. Cecal intubation time (CIT), cecal intubation rate (CIR), and bowel preparation score were also evaluated. Review Manager (RevMan) version 5.3.0 was used to perform statistical analysis. RESULTS: Eight RCTs involving 2059 patients fulfilled the selection criteria. Meta-analysis suggested that OSS significantly increased the PDR (47.34% vs. 40.14%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.24, P = 0.01) and ADR (44.60% vs. 38.14%, RR 1.17, 95% CI 1.03-1.33, P = 0.01) during colonoscopy. Subgroup analysis showed that the beneficial effects of OSS on PDR and ADR were consistent among patients with mean age >55 years and with body mass index <25 kg/m2 receiving outpatient colonoscopy, morning colonoscopy, and the 2-L bowel preparation protocol. Meanwhile, patients receiving OSS had a beneficial bowel preparation score. CONCLUSION: Compared with polyethylene glycol-based regimens, the OSS bowel preparation regimen significantly increased the PDR and ADR in patients undergoing colonoscopy.

Bidirectional associations between parenting styles and conduct problems in Chinese preschool children: the Shenzhen Longhua Child Cohort Study.

The bidirectional associations between parenting styles and conduct problems in Chinese children attending preschools were rarely discussed. A study covering 171 preschools in Longhua District of Shenzhen, China was conducted among children when they first attended preschools. Parents of children reported the self-perceived parenting styles and their children's conduct problems using validated questionnaires. The bidirectional associations between parenting styles and conduct problems in children were assessed using multivariate linear or logistic regressions in both cross-sectional and cohort settings. In cross-sectional settings, the bidirectional associations were present in all dimensions of parenting styles with children's conduct problems. After 1.01 years of follow-up, increases in parenting dimensions of rejection, control attempts, and favoring subject were significantly associated with children's conduct problems at follow-up, while increases in emotional warmth of parents significantly reduced such risk. In addition, parents of children who had conduct problems at baseline but regressed to normal at follow-up showed decreased scores in negative parenting dimensions. In contrast, among children who developed conduct problems during the study period, the scores of rejection and favoring subject in their parents have increased significantly, while the scores of emotional warmth have decreased. Parent-to-child effect was similar between fathers and mothers, while child-to-parent effect was stronger in fathers than that in mothers. In order to stop the negative feedback loop between poor parenting styles and children's conduct problems, our study underscored the importance of intervention not only in parents but also in their children.

High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach.

CYP-mediated fast metabolism may lead to poor bioavailability, fast drug clearance and significant drug interaction. Thus, metabolic stability screening in human liver microsomes (HLM) followed by metabolic soft-spot identification (MSSID) is routinely conducted in drug discovery. Liver microsomal incubations of testing compounds with fixed single or multiple incubation time(s) and quantitative and qualitative analysis of metabolites using high-resolution mass spectrometry are routinely employed in MSSID assays. The major objective of this study was to develop and validate a simple, effective, and high-throughput assay for determining metabolic soft-spots of testing compounds in liver microsomes using a single variable incubation time and LC/UV/MS. Model compounds (verapamil, dextromethorphan, buspirone, mirtazapine, saquinavir, midazolam, amodiaquine) were incubated at 3 or 5 µM with HLM for a single variable incubation time between 1 and 60 min based on predetermined metabolic stability data. As a result, disappearances of the parents were around 20-40%, and only one or a few primary metabolites were generated as major metabolite(s) without notable formation of secondary metabolites. The unique metabolite profiles generated from the optimal incubation conditions enabled LC/UV to perform direct quantitative estimation for identifying major metabolites. Consequently, structural characterization by LC/MS focused on one or a few major primary metabolite(s) rather than many metabolites including secondary metabolites. Furthermore, generic data-dependent acquisition methods were utilized to enable Q-TOF and Qtrap to continuously record full MS and MS/MS spectral data of major metabolites for post-acquisition data-mining and interpretation. Results from analyzing metabolic soft-spots of the seven model compounds demonstrated that the novel MSSID assay can substantially simplify metabolic soft-spot identification and is well suited for high-throughput analysis in lead optimization.